examining the effect of ketamine on glutamate/glutamine cycling

Conditions: Depression

Summary: this study is looking at the mechanisms underlying the behavioral effects of ketamine in healthy and depressed individuals.


Eligibility criteria:
healthy group inclusion criteria: * male or female between the ages of 21-65 years. * able to provide written informed consent. * able to read and write english. exclusion criteria: * personal or first-degree family member with history of mood, anxiety, or psychotic axis i dsm-iv disorders confirmed after comprehensive psychiatric evaluation. * any history of serious medical or neurological illness. * any signs of major medical or neurological illness on examination or as a result of ecg screening or laboratory studies. * lifetime history of psychoactive substance or alcohol dependence or substance or alcohol abuse (other than nicotine or caffeine abuse), or drinking more that 5 drinks/week during the last year. * abnormality on physical examination. * a positive pre-study (screening) urine drug screen or, at the study physician's discretion on any drug screens given before the scans. * pregnant or lactating women or a positive urine pregnancy test for women of child-bearing potential at screening or prior to any imaging day. * subjects who test positive for hiv or viral hepatitis (hepatitis b and/or c) * has received either prescribed or over-the-counter (otc) centrally active medicine or herbal supplements within the week prior to the mri scan. * any history indicating learning disability, mental retardation, or attention deficit disorder. * known sensitivity to ketamine. * body circumference of 52 inches or greater. * body weight of 280 pounds or greater. * history of claustrophobia. * presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-mri screening questionnaire. * donation of blood in excess of 500 ml within 56 days prior to dosing. * history of sensitivity to heparin or heparin-induced thrombocytopenia. * resting blood pressure lower than 90/60 or higher than 150/90,or resting heart rate lower than 45/min or higher than 100/min. depression group inclusion criteria: * male or female between the ages of 21-65 years. * able to provide written informed consent. * current mdd single episode (296.2x) or recurrent (296.3x), as determined by the structured clinical interview for dsm-iv (scid) patient edition * montgomery asberg depression rating scale (madrs) score of 18 or higher at baseline and start of first 13c-mrs. * quick inventory of depressive symptoms - self-report (qids-sr16) score of 19 or higher at baseline and start of first 13c-mrs. * no psychotropic medications for 2 or more weeks (4 weeks for fluoxetine) prior to first 13c-mrs. * be able to understand and speak english. exclusion criteria: * patients with a history of dsm-iv-tr diagnosis of bipolar disorder or schizophrenia or schizoaffective disorder or currently exhibiting psychotic features associated with their depression; dementia or suspicion thereof, is also exclusionary. * first-degree family member with history of schizophrenia or any other psychotic disorder. * serious suicide or homicide risk, as assessed by evaluating clinician; a serious suicide risk will be considered an inability to control suicide attempts, imminent risk of suicide in the investigator's judgment, or a history of serious suicidal behavior, which is defined using the columbia-suicide severity rating scale (c-ssrs) as either (1) one or more actual suicide attempts in the 3 years before study entry with the lethality rated at 3 or higher, or (2) one or more interrupted suicide attempts with a potential lethality judged to result in serious injury or death. * substance abuse or dependence during the 12 months prior to screening. * any history of serious medical or neurological illness. * any signs of major medical or neurological illness. * abnormality on physical examination. a subject with a clinical abnormality may be included only if the study physician considers the abnormality will not introduce additional risk factors and will not interfere with the study procedure. * a positive pre-study (screening) urine drug screen or on any drug screens given before the scans. * pregnant or lactating women or a positive urine pregnancy test for women of childbearing potential at screening or prior to any imaging day. * any history indicating learning disability, or mental retardation. * known sensitivity to ketamine. * body weight of 280 pounds or greater. * history of claustrophobia. * presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-mri screening questionnaire. * donation of blood in excess of 500 ml within 56 days prior to dosing. * history of sensitivity to heparin or heparin-induced thrombocytopenia. * resting blood pressure lower than 90/60 or higher than 150/90,or resting heart rate lower than 45/min or higher than 100/min.